Transcription
fat. >> Visceral fat. Fat. Visceral fat. Visceral fat. Visceral fat. >> High amount of visceral fat. >> Fat is a word we've learned to flinch at because it conjures images of overindulgence, of sickness, and of shame. But what if our discomfort with fat wasn't just cultural? What if it was biological? Indulge me while I take this a step further. What if fat creates your mood? What if fat could cause depression? I know it sounds dramatic and you're probably skeptical, but guess what? The biology is even more dramatic because fat isn't just passive storage. It's an endocrine organ. This means it's a hormone factory. It sends signals out across the body. Signals that can cross the blood-brain barrier and change brain chemistry, shift mood, change how we feel. And today we're delving into brand new and exciting scientific research that takes that hypothesis that fat can cause depression a step closer to biological fact. Now, I want to be clear. This isn't about shame. This isn't about blame. This is about understanding one of the most misunderstood systems in our body and finding a path forward. Stick with me until the end of this video and I really hope you'll leave feeling informed, inspired, empowered, and maybe just a little bit mentally lighter, too. Let's go.
Increase susceptibility to stress. Vicious cycle between obesity and depression. Individuals with obesity are twice as likely to experience depression. Westernized diet induced depression-like behavior. Transplantation of visceral fat alone. Let's get mechanistic. The paper I want to chat about reveals how molecular packages called extracellular vesicles or EVs for short can travel from visceral fat, inflammatory fat in your abdominal cavity, through the bloodstream and into the brain where they alter the function of specific brain areas, increase susceptibility to stress, and can even promote depression.
But first, for some population data, human context, depression and obesity, they are known to be highly what's called comorbid, meaning they often occur together. Individuals with obesity are twice as likely to experience depression as those of a normal healthy weight. Moreover, those diagnosed with depression are at a 58% higher risk of developing obesity down the line. This is in part due to the adverse effects of certain anti-depressant medications which can cause weight gain. And what this does, as maybe you can see, it establishes a potential vicious cycle between obesity and depression. A descending spiral with yes, social, psychological, pharmarmacological, and metabolic components. But one big question remains unanswered. How? How does fat tissue contribute to depression? Now, this is a very difficult question to answer in humans. You can't perform controlled human trials to answer that question. And the social baggage of living with obesity in modern society. It introduces many psychosocial confounders. So, what do we have to do? We need to turn to animal models. We'll return to the human story, I promise. But first, let's get mechanistic.
In this study, researchers demonstrated that a high-fat, high-sugar, westernized diet designed to cause obesity in animals in mice also induced depression-like behavior. And if you're curious and want to know the methods on how scientists actually measure depression in animals using validated tests like the tail hanging test, see more details at staycuriousmetabolism.com and in the associated newsletter. You can check the links below. Anyway, here's where things get extra interesting. To test the hypothesis that visceral fat specifically was responsible for the depression-like behavior in these animals, researchers transplanted visceral fats from mice on that obesogenic diet, the obese mice, into normal, healthy mice. They literally transplanted the visceral fat. And the amount of the fat transplanted was pretty small. It was enough to transmit a biochemical signal, but not enough to make the transplant recipient mice themselves obese. We weren't giving these mice a visible beer gut, so to speak. And interestingly, compared to the control group that received fat from lean mice, the mice that received visceral fat from the obese donors similarly exhibited depression-like behavior. And this suggests, look, just internalize this for a moment. This suggests that transplantation of visceral fat alone is sufficient to cause depression. But how? What the researchers found next was truly mind-boggling to me.
Now, I promise in the rest of this video, we're going to dive into the detailed mechanisms, what it means for you, and I'm going to give you practical, specific lifestyle suggestions. But first, I want to tell you about the sponsor of this video, Chapter. Chapter isn't a pill or a supplement. It's a program, a practical program to help older adults navigate the complex, mind-boggling maze that is Medicare. It shouldn't be this complicated. And this, this is relevant to this video since 14% of adults over 65 develop depression at some point in their life. And the right coverage is important to getting the right support. And the right health insurance fit for you doesn't just give you the best care, it saves money. Chapter program users save on average $1,100 per year. And that great care tailored to your unique needs actually increases your chances of living longer, longer, and happier. If you want more on that, see this letter chapter. It's fully independent and their guides get on the phone with you, human-to-human, to help you find the plan that fits you. So, if you or someone you care about could benefit from this, please call our helpline that we've set up, 815-STAYCURE, as in 815-STAY-CURIOUS. Stay-CURE. That's 815-782-9287. Thanks for listening. And now back to fat, the brain and extracellular vesicles, which are arguably less complicated than health insurance.
Visceral fat tissue releases tiny molecular packages called extracellular vesicles. I mentioned these earlier, these EVs. They're double membrane spheres containing biological cargo like protein and nucleic acids. We'll tell you specifically what they're carrying later. And these extracellular vesicles, these EVs, circulate throughout the body and act as chemical messengers, chemical mailmen between organs and tissues. And in this case, the EVs from visceral fat traveled through the bloodstream and targeted specific brain regions like the hippocampus where they impaired neuronal function, reduced levels of brain-derived neurotrophic factor BDNF and disrupted synaptic function in the brain. This is thought to be the mechanism by which visceral fat can contribute to depression. But there's one more nuance we need to add to complete our mechanistic picture before we get back to the human. What is inside these extracellular vesicles that actually triggers the depression cascade? The researchers identified a particular microRNA called uncreatively MIR 145P as the key molecule. If extracellular vesicles are like envelopes, MIR 145P is the letter inside. It's a biochemical message from visceral fat to the brain, one that impairs neurons and promotes depression. And notably, MIR 145P was also found to be significantly upregulated in humans with obesity, lending credibility to the idea that this is not just a mouse phenomenon, but a plausible biological mechanism by which visceral fat in humans could causally contribute to depression in humans as well.
So, I know that was a lot. Let's step back and summarize. Visceral fat releases extracellular vesicles. These contain MIR 145P, the letter within the envelope. These extracellular vesicles travel to the brain, impair neuron function, reduce BDNF, and ultimately they can promote depression. Isn't that fascinating? But let's evolve our story further by talking about MIR 145P as a biomarker for depression in humans. Now, depression is defined, as you may intuit it, by a clinical diagnosis. It's a clinical diagnosis. That means it's not identified through blood tests or brain scans, but rather through a person's symptoms and self-report. Still, that doesn't mean there aren't underlying metabolic changes involved in depression. And if there are, and there are, it opens up the door to developing biomarkers for depression. And ideally, such biomarkers would be predictive, meaning they could help identify people who are likely to develop depression or have worsening depression even before the symptoms appear, before the symptoms worsen. And MIR 145P, this microRNA in those extracellular vesicles might be such a predictive biomarker. For instance, in one study of patients hospitalized for strokes, higher levels of MIR 145P at the time of admission for the stroke were found to be an independent risk factor for developing depression later on in life, a condition called post-stroke depression. This form of depression in humans is surprisingly common, affecting about one in three stroke survivors. And even more strikingly, there appeared to be a dose-response relationship, meaning the higher level of MIR 145P there was in the patient, the worse the depression symptoms would be later on, as measured by the Hamilton depression rating scale. So, if we integrate this new information with what we learned about the mechanisms, we start to develop a clearer picture. MIR 145P isn't just a passive bystander. It may be a signal and a consequence of severe metabolic stress, excess visceral fat or a stroke that triggers a cascade of events leading to changes in the brain and depression.
Now, I want to take a brief but relevant tangent to step beyond depression and discuss the potential role of MIR 145P in Alzheimer's disease. Why? Well, because it's freaking fascinating for one, but also because it highlights a recurring theme we've often discussed on this channel. Chronic metabolic diseases, they share underlying pathological drivers. They share common roots. And yes, these roots manifest differently in different people. For me, it manifested in inflammatory bowel disease. For other people, it manifests as obesity. Others depression. Others Alzheimer's disease. And we tend to classify these diseases into distinct categories. But many of the same molecular and metabolic disruptions that contribute to say, mental illness, they also play roles in neurodegenerative diseases including Alzheimer's. In fact, remember I said hippocampus, that was the or that is the region that's primarily affected severely in Alzheimer's disease. And MIR 145P appears to be a case in point where the same molecule has roles in different diseases. It has been proposed that MIR 145P may contribute to Alzheimer's disease by worsening brain insulin resistance and promoting the formation of neurofibrillary tangles in the brain, phosphotau tangles which are a defining hallmark of Alzheimer's disease. So in one study, for example, researchers found that MIR 145P inhibited a protein called pin 1. You don't really need to know that, but it was called pin 1, which itself is neuroprotective, supports brain metabolism and insulin sensitivity in the brain and slows the neuropathological progression of Alzheimer's disease. But when researchers blocked MIR 145P, PIN activity increased and this led to improvements in brain metabolism, decreased inflammation and decrease in phosphotau generation and compellingly, improvements in learning and memory in rodent models. I know I'm saying a lot. I'm spewing a lot at you. It's because I'm excited. But all of this suggests in a nutshell that MIR 145P, this molecule we're talking about, could be a molecular link between visceral fat, depression, neurodegeneration, Alzheimer's disease, and impaired metabolic health more broadly. Its influence appears to cut across disease boundaries, reinforcing the idea, the broader theme that many modern illnesses may have different expressions in different people, but they share a common underlying metabolic dysfunction.
Now, we get to the question, how do you reduce MIR 145P? Well, apologies for the lack of creativity here, but if visceral fat is the primary production site of MIR 145P, then the answer is fairly straightforward. Reduce visceral fat. For example, in one longitudinal study of human patients following weight loss after bariatric surgery, there was a 67% reduction in MIR 145P levels. Now, it's worth noting that visceral fat loss generally tracks along with overall body fat loss. So, if you have excess weight to lose, any effective weight loss approach is likely to yield the biggest metabolic returns in visceral fat loss and potentially brain health as a knock-on effect. That said, there may be a few specific food strategies that can more directly target visceral fat. The data are early, but for instance, in a randomized control trial comparing two different low-carbohydrate diets, there is preliminary evidence suggesting that green tea and a lesser-known plant called wolfia globosa might actually preferentially reduce visceral fat. The researchers behind this randomized control trial proposed that certain components in these foods may interact with tissue-specific metabolic pathways, particularly those in visceral fat. I'm not going to go into details in this video, but you can see this other video if you want a breakdown of that randomized control trial.
So, wrapping up, I want to give you my final thoughts, the big picture. Visceral fat, it's not just a passive storage site. It's metabolically active and capable of sending biochemical signals to the brain that can influence mood and brain health. Through molecules like the microRNA MIR 145P, we see how excess body fat can contribute to depression or Alzheimer's disease. But the good news, these pathways are modifiable. Reducing visceral fat, whether through diet, lifestyle, or other targeted interventions might not only improve metabolic markers peripherally, but it could also protect your mind. Better metabolism, better mental health. It's one system. It's not separated in silos. Tell me what you learned from this video. Tell me what you want to learn more. And I really appreciate you. If you would subscribe here, subscribe to the Stay Curious Metabolism newsletter. We're going to keep learning based on what I find interesting. And I also love your feedback. So tell me what more you want to learn. Stay curious. I hope you found this eye-opening.